The need for biomaterials in orthopedic and dental applications has increased as the world population ages. A significant amount of research into biomaterials for orthopedic and dental uses has attempted to address the functional criteria for orthopedic and dental reconstruction within the human body. Biomaterials useful for orthopedic and dental reconstructions must have high strength, must be able to be immediately affixed to the situs for reconstruction, must bond strongly to bone, and must give rise to strong, highly resilient restorations.
Among the materials used for orthopedic and dental restorative purposes are bone cements based upon acrylic species such as polymethyl methacrylate (PMMA), bisphenol-A-diglycidyl methacrylate (bis-GMA), triethyleneglycol dimethacrylate (TEGDMA), diurethane dimethacrylate (DUDMA), bisphenol-A-ethoxy methacrylate (bis-MMA), and related compositions. Such materials usually are capable of convenient delivery to the site of restoration and can be formed so as to be moldable and to have reasonable degrees of affinity for bony tissue. Typically, these materials are provided in two package systems consisting of paste/paste or liquid/powder materials to be mixed at the time of use to yield a hardened composite. These systems are commonly initiated under room temperature conditions using a peroxide and a reducing agent, or the like. Photosensitive systems, generally supplying quinines and the like as photoinitiators are also known.
In general, however, the materials that are added to the composition to initiate polymerization under room temperature conditions, such as peroxides, photoinitiators, other free radical generators (azo compounds, persulfates, phosphines, etc.), and certain reducing agents (amines, ascorbates, metal salts, etc.) can prematurely initiate polymerization. Decomposition can result if the materials are stored too long or exposed to heat and/or light. Photochemical and thermal degradation of peroxides have both shown to yield radicals that prematurely initiate polymerization in (meth)acrylate based systems. This phenomena is typically controlled by atmospheric oxygen and/or through the addition of UV stabilizers and free radical scavengers such as butylhydroxytoluene (BHT), hydroquinone (HQ), methyl ether hydroquinone (MEHQ), etc. However, oxidation of the accelerating agents decreases the efficiency of the system and ultimately can result in the failure of the system to polymerize upon mixing. Unfortunately, the addition of most commercial antioxidants will further inhibit polymerization.
U.S. Pat. No. 5,941,037 to Hallock, et al. disclose a modified anionic hydrotalcite particulate used as an oxygen scavenger in the packaging of food products. The particulate containing oxygen scavenging composition absorbs oxygen from the interior of a container without adversely affecting color, taste, or smell of the packaged product. Hallock does not teach the use of these amino acids alone or without the aid of hydrotalcite to stabilize polymerizable materials.
U.S. Pat. No. 4,837,115 to Igarashi, et al. disclose a thermoplastic polyester vessel with a flavor retaining property for use in food packing. The polyester reduces the concentration of acetaldehyde contained in a gas barrier thermoplastic polyester. It also improves the flavor from the gas barrier thermoplastic polyester. The acetaldehyde concentration in a heat-formed vessel wall is reduced when there is a polyamide having a specific terminal amino group. Yet, Igarashi, et al. only teaches the use of the polyester composition to a container and not the contents therein.
U.S. Pat. No. 6,162,419 to Perricone, et al. disclose stabilized compositions of ascorbic acid, ascorbic acid salts, ascorbyl fatty acid ester or their salts for dermatological use. Ascorbic containing acid compositions deteriorate by combining with oxygen in the atmosphere to yield inactive forms. The patent discloses no teaching that cysteine is useful to prevent polymerization.
U.S. Pat. No. 6,136,294 to Adjei, et al. disclose an aerosol formation containing a particulate drug, a propellant, and a stabilizing agent selected from an amino acid, amino acid derivation, or a mixture thereof. Amino acids are used to stabilize the aerosol formulation so that it does not cream, settle, or flocculate after agitation or delivery of the drug. The amino acids are not used to prolong shelf life or prevent polymerization.
U.S. Pat. No. 6,168,655 to Nohr, et al. disclose stabilizers for ink compositions containing a colorant. According to this patent, cysteine can be used as a reducing agent when added to a substrate such as paper, glass, or wood. However, it is not used to stabilize and prolong the shelf life of a polymerizable system.
Accordingly, there is a need to provide a method of stabilizing orthopedic materials to inhibit or minimize the degradation of specific components to improve shelf life and prevent autopolymerization during storage without the introduction of a toxic moiety or a species which inhibits polymerization upon mixing.
There is a further need to provide a stabilizer that reduces the degradation of the constituents of orthopedic materials while maintaining properties such as set-time, degree of functional group conversion, and mechanical properties that tend to change upon aging.